This is a revision of the competing continuation of R01-MH43454. This application seeks five additional years of support to continue the PI's research program on the neural substrates of affective style and emotion regulation. Individual differences in affective style and emotion regulation determine variation in stress responsivity and vulnerability to mood, anxiety and externalizing disorders. The broad goal of this application is to further understand the neural circuitry underlying individual differences in emotion regulation and to determine the relation between the neural bases and biobehavioral correlates of voluntary and automatic forms of the regulation of negative and positive affect. Work is proposed that also extends this work to late adolescents who are part of a longitudinal sample that we have been following with imaging and behavioral measures for the past 5 years and on whom we have behavioral and hormonal data since birth. One major study will examine relations between voluntary and automatic regulation of both negative and positive emotion to determine if skill in one predicts skill in the others, and to determine if there is overlapping or orthogonal neural substrates of each, including activation and connectivity measures. We will specifically address the question of whether participants who are skilled at down-regulating negative affect are also skilled at upregulating positive affect. As part of this study, we will also examine relations between the regulation of picture-induced negative affect and thermal pain-induced negative affect. Another study will examine relations between individual differences in working memory (WM) capacity and emotion regulation. In addition to tasks assessing emotion regulation, participants will be given a working memory task (n-back) in the scanner and activated regions of overlap in the prefrontal cortex during the WM and emotion regulation tasks will be determined. In addition, we will examine relations between working memory capacity and automatic and voluntary emotion regulation. Finally, using a sample derived from the Wisconsin Study of Families and Work, we will examine relations between individual differences in emotion regulation and symptoms and diagnoses of psychopathology. We will also relate neural and psychophysiological measures of emotion regulation to the longitudinal corpus of data already collected on these participants. This work will provide critical new information on the neurobiology of affective style. These new data will further our understanding of endophenotypes of affective processing that are associated with vulnerability to psychopathology. PUBLIC HEALTH RELEVANCE: Vulnerability to mood and anxiety disorders appears to be at least in part determined by a person's capacity to regulate his or her emotions. The ability to recover following a negative event and to reappraise a situation to make it less threatening is of great benefit in adaptively responding to the environment. This project is focused on identifying the brain mechanisms that determine our ability to regulate our emotions, both to down-regulate our negative emotions and to upregulate our positive emotions. This work has significant implications for developing new psychological and pharmacological treatments for mood and anxiety disorders.